Clinical Trials Register

Summary
EudraCT Number:	2017-003595-30
Sponsor's Protocol Code Number:	IRFMN-7358
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2021-06-18
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Italy - Italian Medicines Agency

A.2

EudraCT number

2017-003595-30

A.3

Full title of the trial

Treat_CCM Clinical Trial. A multicenter randomized clinical trial on Propranolol in Cerebral Cavernous Malformation

Studio multicentrico, randomizzato sul propranololo nella Malformazione Cavernosa Cerebrale (CCM)

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

Clinical study to evaluate the efficacy of propranolol in familial Cerebral Cavernous Malformation

Studio per valutare l'efficacia del propranololo nel trattamento dei pazienti con CCM famigliare

A.3.2

Name or abbreviated title of the trial where available

Treat_CCM Clinical Trial.

A.4.1

Sponsor's protocol code number

IRFMN-7358

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	IRCCS- ISTITUTO DI RICERCHE FARMACOLOGICHE MARIO NEGRI
B.1.3.4	Country	Italy
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	AIFA - Italian Medicines Agency
B.4.2	Country	Italy
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	IRCCS ISTITUTO DI RICERCHE FARMACOLOGICHE MARIO NEGRI
B.5.2	Functional name of contact point	DIPARTIMENTO DI RICERCA CARDIOVASCO
B.5.3	Address:
B.5.3.1	Street Address	VIA LA MASA, 19
B.5.3.2	Town/ city	MILANO
B.5.3.3	Post code	20156
B.5.3.4	Country	Italy
B.5.6	E-mail	roberto.latini@marionegri.it

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	INDERAL - 40 MG COMPRESSE 30 COMPRESSE
D.2.1.1.2	Name of the Marketing Authorisation holder	ASTRAZENECA S.P.A.
D.2.1.2	Country which granted the Marketing Authorisation	Italy
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Propranololo
D.3.2	Product code	[C07AA05]
D.3.4	Pharmaceutical form	Tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	PROPRANOLOLO
D.3.9.1	CAS number	525-66-6
D.3.9.2	Current sponsor code	NA
D.3.9.3	Other descriptive name	PROPRANOLOL
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	range
D.3.10.3	Concentration number	40 to 320
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Cerebral Cavernous Malformation (CCM)

Malformazione Cavernosa Cerebrale (CCM)

E.1.1.1

Medical condition in easily understood language

The term refers to a familial decease characterized by mulberry-shaped abnormal blood vessels in the brain or spine.

Una patologia familiare, caratterizzata da malformazioni vascolari (angiomi) nel cervello o nel midollo spinale.

E.1.1.2

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	23.0
E.1.2	Level	PT
E.1.2	Classification code	10071747
E.1.2	Term	Cerebral cavernous malformation
E.1.2	System Organ Class	10010331 - Congenital, familial and genetic disorders

E.1.3

Condition being studied is a rare disease

Yes

E.2 Objective of the trial

E.2.1

Main objective of the trial

Test whether a chronic treatment with propranolol will reduce the burden of cerebrovascular lesions, of clinical events symptoms in patients with familial CCM

Valutare l'efficacia del propranololo nella riduzione delle lesioni cerebrovascolari e degli eventi clinici nei pazienti CCM familiare.

E.2.2

Secondary objectives of the trial

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1.Patients with Familial cerebral cavernous malformations (FCCM);
2.history of clinical symptoms or events: intracerebral hemorrhage, stroke, permanent or transient focal deficits, seizures, disability or any other neurological symptom supposedly related to CCM;
3.age of at least 18 years.
4.Written informed consent to participate in the study prior to any study procedures.

1.Pazienti CCM familiare sintomatica;
2.storia clinica con sintomatologia CCM o eventi clinici: emorragia intracerebrale, ictus, deficit focale permanente o transitorio, epilessia, disabilità o qualsiasi altro sintomi neurologici associati a CCM;
3.individui adulti (> 18 anni);
4.consenso informato firmato per la partecipazione allo studio, prima del suo inizio.

E.4

Principal exclusion criteria

1.Implanted pacemaker or any other condition preventing the MRI exam;
2.bradycardia, 2nd or 3rd degree AV block or symptomatic hypotension;
3.unstable diabetes;
4.severe asthma;
5.liver and/or renal failure;
6.current use of verapamil or diltiazem for risk of excessive bradycardia;
7.previous brain surgery (within 6 months);
8.known hypersensitivity to study drug (propranolol or any of the ingredients)
9.pregnant or lactating women or women of childbearing potential who are not protected from pregnancy by an accepted method of contraception
10.participation to another clinical trial;
11.inability to cooperate with the trial procedures.

1.Pazienti portatori di pacemaker o qualsiasi altra condizione incompatibile con l’esecuzione di una tecnica di immagine basata sulla risonanza magnetica;
2.bradicardia o blocco arterioventricolare di 2° o 3° grado, ipotensione sintomatica;
3.diabete instabile;
4.asma bronchiale grave;
5.insufficienza epatica o renale;
6.indicazione per verapamil e diltiazem;
7.ipersensibilità nota al farmaco in sperimentazione (propranololo e/o suoi eccipienti);
8.chirurgia cerebrale pregressa (<6 mesi);
9.gravidanza e allattamento; donne in età fertile non protette da misure anticoncezionali adeguate;
10.partecipazione ad un altro studio clinico;
11.incapacità a seguire le procedure dello studio.

E.5 End points

E.5.1

Primary end point(s)

New occurrence of clinical events CCM-related, that is intracerebral hemorrhage (ICH) and focal neurological deficits (FND) including seizures.

incidenza di nuovi eventi clinici correlati con la CCM come emorragia intracerebrale e/o deficit neurologici focali, incluse le crisi epilettici.

E.5.1.1

Timepoint(s) of evaluation of this end point

24 MONTHS

24 MESI

E.5.2

Secondary end point(s)

Microvascular hemorrhages as assessed by brain MRI.; Clinical outcomes such as global cognitive function, global disability and health related quality of life.; Different vascular lesion characteristics such as diameter, length, and location assessed by MRI.

Emorragie micro-vascolari, identificate nel tessuto cerebrale con MRI. ; Funzione cognitiva globale, disabilit¿ globale e qualit¿ di vita.; Caratteristiche delle diverse malformazioni vascolari (diametro, lunghezza e sede) valutate con MRI.

E.5.2.1

Timepoint(s) of evaluation of this end point

24 months; 24 months; 24 months

24 mesi; 24 mesi; 24 mesi

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

E.8.2.3

Other

Yes

E.8.2.3.1

Comparator description

TERAPIA STANDARD

STANDARD CARE

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

Information not present in EudraCT

E.8.7

Trial has a data monitoring committee

Yes

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

LVLS

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2018-02-21

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2018-02-06

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2021-12-31

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